RESUMO
Sodium valproate after chronic intragastric administration in the high dose of 100-200 mg/kg eliminates generalized clonic-tonic pentylenetetrazol seizures in 100 % of rats, but only in 33-57 % of rats it prevents local clonic kindling seizures. Strong sedation is induced by the specified doses of sodium valproate. The combined oral chronic administration of phenylephrine in threshold, noneffective alone dose of 0.2 mg/kg and sodium valproate in high doses of 100 mg/kg and 200 mg/kg potentiates anticonvulsive action of sodium valproate, because prevents both clonic-tonic kindling. seizures in 100 % of rats and clonic kindling seizures in 86-100 % of rats, and also it increases in 1.7-1.9 times anticonvulsive activity of valproate. The specified combinations of sodium valproate with phenylephrine do not produce the sedative side effect. The basis of the mechanism of potentiation of anticonvulsive action and elimination of sedative action of sodium valproate in high doses is the stimulation of gastric mucosa afferents by phenylephrine.
Assuntos
Anticonvulsivantes/farmacologia , Excitação Neurológica/efeitos dos fármacos , Fenilefrina/farmacologia , Convulsões/tratamento farmacológico , Simpatomiméticos/farmacologia , Ácido Valproico/farmacologia , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/fisiologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Pentilenotetrazol , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/fisiopatologia , Vigília/fisiologiaRESUMO
Two groups of substances capable of selectively blocking the NMDA and AMPA/kainate receptors in experiments on intact animals were found in a series of bis-ammonium compounds with adamantyl radicals. The selective NMDA receptor blockers (IEM-1754, IEM-1755, IEM-1752), as well as the reference agents MK-801 and memantine, produced anticonvulsant, anti-ischemic, and antihypoxant effects and prevented the loss of experimental animals from toxic doses of NMDA. The selective AMPA/kainate receptor blockers (IEM-1553, IEM-1751, IEM-1592, and DNQX)) also produced the anticonvulsant, anti-ischemic, and antihypoxant effects, but did not prevent from the loss of animals caused by the toxic doses of NMDA. The maximum activity was observed for IEM-1754, the activity of which exceeded that of MK-801 (by a factor of 5-10) and memantine (by a factor of 300-800) in all the test objects.